This project is concerned with (a) analyses of the genetic diversity of Trypanosoma cruzi and its implications to the epidemiology, course, and diagnosis of Chagas' disease; (b) the development of high resolution flow cytometry instrumentation for biomedical research; and (c) the utilization of flow cytometry and low light level video microscopy for the analyses of infectious agents. We have demonstrated that DNA variants of T. cruzi occur at low frequency from a single-cell isolate clone stock. These variants are being characterized. Environmental parameters such as temperature can destabilize the DNA of T. cruzi resulting in the appearance of variant stocks. Drug and radiation-induced T. cruzi mutants have been produced which are resistant to tubercidin, an adenosine analogue. These mutants are being characterized in an attempt to determine the genetic basis for drug resistance.